Neuropeptide Y (hereinafter referred to as NPY) is a peptide which consists of 36 amino acid residues and was isolated from porcine brain in 1982. NPY is widely distributed in the central nervous system and peripheral tissues of humans and animals.
It has been reported that NPY possesses a stimulatory action on food intake, an anti-seizure activity, a learning-enhancing action, an anti-anxiety activity, an anti-stress activity, etc. in the central nervous system, and it may be pivotally involved in central nervous system diseases such as depression, Alzheimer's disease, Parkinson's disease. NPY is thought to be involved in cardiovascular diseases, since it induces a contraction of smooth muscles such as blood vessels or cardiac muscles in peripheral tissues. Furthermore, NPY is also known to be involved in metabolic diseases such as obesity, diabetes, hormone abnormalities (Non-patent Document 1). Therefore, an NPY receptor antagonist is expected as medicine for preventing or treating the above-mentioned various diseases associated with the NPY receptor.
Six subtypes of NPY receptors have now been identified: Y1, Y2, Y3, Y4, Y5, and Y6 (Non-patent Document 2). It has been suggested that the Y5 receptor is at least involved in the feeding behavior and its antagonist is expected as an anti-obesity drug (Non-patent Document 3).
Patent Documents 1 to 4 disclose urea derivatives having structures similar to those of compounds of the present invention and exhibiting an NPY Y5 receptor antagonistic activity, but do not disclose urea derivatives substituted with benzoxazolinone.
Patent Documents 5 to 7 disclose urea derivatives: Document 5, 6 and 7 disclose N-(3,4-dihydro-3-oxo-2H-1,4-benzoxazin-6-yl)-N′-[2-[ethyl(3-methylphenyl)amino]ethyl]-urea, N-[3-(diethylamino)propyl]-N′-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-urea and N,N″-1,6-hexanediylbis[N′-(2,3-dihydro-2-oxo-6-benzoxazolyl)]-urea, respectively. None of these documents, however, refer to an NPY Y5 receptor antagonistic activity.    [Non-patent Document 1] Trends in Pharmacological Sciences 1994; 15: 153    [Non-patent Document 2] Trends in Pharmacological Sciences 1997; 18: 372    [Non-patent Document 3] Peptides 1997; 18: 445    [Patent Document 1] WO01/037826    [Patent Document 2] JP2001-122865    [Patent Document 3] WO02/022592    [Patent Document 4] WO02/049648    [Patent Document 5] WO05/103018    [Patent Document 6] JP03/096056    [Patent Document 7] EP45892